Study of Efficacy and Safety of INC424 in Regularly Transfused Patients With Thalassemia.

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02049450
First received: January 28, 2014
Last updated: NA
Last verified: January 2014
History: No changes posted
  Purpose

Patients with severe thalassemia (thalassemia major) present with severe anemia that requires life-long transfusion therapy, spleen enlargement that may lead to increased transfusion requirement, and other serious complications as early death, growth retardation, bone deformations and iron overload due to blood transfusions. Splenectomy can significantly reduce transfusion requirement in thalassemia patients, but it is associated with an increased risk of serious complications such as sepsis and thrombosis. Preliminary preclinical and clinical data suggest that JAK2 inhibition, by reducing spleen size, may improve hemoglobin levels, thereby eliminating the need for splenectomy and reducing transfusion requirement and related iron overload.


Condition Intervention Phase
Thalassemia Major
Drug: INC424 (ruxolitinib)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Arm, Multicenter, Phase IIa Study to Explore the Efficacy and Safety of Ruxolitinib (INC424) in Regularly Transfused Patients With Thalassemia

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percent change of RBC (Red Blood Cell) transfusion requirement [ Time Frame: week 6 to week 30 ] [ Designated as safety issue: No ]
    Percent change in RBC transfusion requirement between week 6 and week 30 and the baseline period between week -24 and the day before first study drug administration.


Secondary Outcome Measures:
  • Change of spleen volume [ Time Frame: baseline, week 12, week 30 ] [ Designated as safety issue: No ]
    Change of spleen volume from baseline measured by MRI or CT at week 12 and week 30

  • Change of pre-transfusion hemoglobin level [ Time Frame: baseline, week 1,2,3,4,6,12,18,24,30 ] [ Designated as safety issue: No ]
    Change of pre-transfusion hemoglobin level from baseline at each post-baseline visit

  • Change of spleen length [ Time Frame: baseline, week 1,2,3,4,6,12,18,24,30 ] [ Designated as safety issue: No ]
    Change of spleen length from baseline over time measured by palpation

  • Pharmacokinetics (PK) parameters of Cmin and C max [ Time Frame: baseline, week 2, 12 ] [ Designated as safety issue: No ]
    C min and C max (1h) of INC424 by actual dose administered

  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: baseline, week 1,2,3,4,6,12,18,24,30 ] [ Designated as safety issue: Yes ]
    Adverse events (AEs), serious adverse events (SAEs), lab results, ECGs, vital signs


Estimated Enrollment: 30
Study Start Date: February 2014
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study Treatment
Approximately thirty regularly transfused adult patients with thalassemia and spleen enlargement.
Drug: INC424 (ruxolitinib)
INC424 oral tablet (5 miligrams)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients 18 years of age or older
  2. Patients with thalassemia on a regular and stable transfusion regimen (at least 2 RBC units within every 4-week interval for 24 weeks prior to Screening) and anticipated to receive the same transfusion regimen during the study.
  3. Patients with spleen enlargement at Screening, defined as spleen palpable below the costal margin and spleen volume of ≥ 450 cm3 as confirmed by MRI (or CT scan in applicable patients).
  4. Patients need to be on iron chelation treatment (deferoxamine or deferasirox) for at least four weeks prior to Screening

Exclusion Criteria:

  1. Splenectomy prior to or planned during the study.
  2. Active serious bacterial, mycobacterial, fungal, parasitic or viral infection which requires therapy (e.g., pneumonia, tuberculosis, systemic mycosis, herpes zoster).
  3. Hemoglobin <65 g/L (<4.0 mmol/L) at Screening.
  4. Platelet count <75×109/L, absolute neutrophils count < 1.5×109/L at Screening.
  5. Estimated MDRD < 30 mL/min/1.73 m2 at Screening.
  6. ALT (SGPT) levels >5 times ULN at Screening.
  7. Hepatocellular disease such as hepatitis B (presence of HBs antigen), hepatitis C (presence of HCV RNA), liver cirrhosis.
  8. HIV positivity

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  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02049450

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02049450     History of Changes
Other Study ID Numbers: CINC424X2201
Study First Received: January 28, 2014
Last Updated: January 28, 2014
Health Authority: Lebanon: Institutional Review Board

Keywords provided by Novartis:
thalassemia, spleen enlargement

Additional relevant MeSH terms:
Beta-Thalassemia
Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on July 22, 2014